Geriatric Pharmacotherapy

Copyright 1998, 2002 The University of Kansas Medical Center
  • Aging Physiology & Pharmacology

    • Limitation of Knowledge:

      • Much of pharmacology practice is based on extrapolation from study of younger or healthier persons.

        • Older populations are under-studied for many drugs in routine use.

        • Concomitant drug use is also an exclusion in many trials of new agents.

        • Retrospective analyses that implicate certain drugs in adverse outcomes are confounded by indication, disease, and population factors.

        • Physically or cognitively frail persons are excluded from randomized drug trials.

    • Pharmacokinetic: Changes Related to Aging: "What the Body Does to the Drug"

      • Absorption the passage of medication into the plasma compartment.

        • Gastrointestinal tract changes seem to be of minor clinical significance.

        • Absorption is impacted by site of administration and formulation of medication. (Remember, Bioavailability is influenced by absorption and by the extent of first-pass metabolism.)
  • Distribution: Important Age-Related Changes:
    • Decrease in Lean Body Mass and Total Body Water; higher concentrations of water soluble drugs.
    • Increase in volume of distribution for lipophilic drugs, such as sedatives that penetrate CNS.

    • Protein binding changes are of modest significance for most drugs, especially at steady-state.

  • Metabolism
    • Liver metabolism:
      • Though liver function tests are unchanged with age, there is an overall decline in metabolic capacity due to decreased liver mass and hepatic blood flow.
      • Metabolic capacity is highly variable; no good estimation algorithm exists.
      • Phase I (oxidation, reduction, hydrolysis) is more likely to decrease with advancing age.
      • Phase II (conjugation) usually unchanged.
  • Excretion
    • Decreased renal blood flow, GFR, tubular secretion, and renal mass.
    • Decreased lean body mass leads to decreased creatinine production; serum creatinine may appear normal even when significant renal impairment exists.
    • A good estimation formula is available:
      • Cr cl=(140-age)(LBW)/creatinine(72)
        multiply by 0.85 for females
  • Pharmacodynamics:  "What the Drug Does to the Body"
  • Generally, lower drug doses are required to achieve the same effect with advancing age.
  • Receptor numbers, affinity, or post-receptor cellular effects may change.
  • Changes in homeostatic mechanisms can increase or decrease drug sensitivity.

  • Homeostenosis:

    • Impaired ability to compensate for physiologic challenges.

    • Some clinically important aging-related changes may interact with medication responses:

      • Blood pressure regulation

        • tendency to orthostatic hypotension.

        • narrowed BP range for adequate CNS perfusion.

        • may not increase heart rate when needed.

      • Thermoregulation

        • impaired reserve against both heat and cold.

      • Volume Regulation

        • decreased reserves of body water.

        • decreased thirst mechanism.

        • decreased maximum urinary concentration.

        • decreased ability to excrete free water load.

Proceed to Adverse Drug Effects (ADEs)
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